Relationship between HIV coinfection, interleukin 10 production, and Mycobacterium tuberculosis in human lymph node granulomas
journal contributionposted on 2020-07-17, 16:36 authored by CR Diedrich, J O'Hern, MG Gutierrez, N Allie, P Papier, G Meintjes, AK Coussens, H Wainwright, RJ Wilkinson
BACKGROUND: Human immunodeficiency virus type 1 (HIV)-infected persons are more susceptible to tuberculosis than HIV-uninfected persons. Low peripheral CD4+ T-cell count is not the sole cause of higher susceptibility, because HIV-infected persons with a high peripheral CD4+ T-cell count and those prescribed successful antiretroviral therapy (ART) remain more prone to active tuberculosis than HIV-uninfected persons. We hypothesized that the increase in susceptibility is caused by the ability of HIV to manipulate Mycobacterium tuberculosis-associated granulomas. METHODS: We examined 71 excised cervical lymph nodes (LNs) from persons with HIV and M. tuberculosis coinfection, those with HIV monoinfection, and those with M. tuberculosis monoinfection with a spectrum of peripheral CD4+ T-cell counts and ART statuses. We quantified differences in M. tuberculosis levels, HIV p24 levels, cellular response, and cytokine presence within granulomas. RESULTS: HIV increased M. tuberculosis numbers and reduced CD4+ T-cell counts within granulomas. Peripheral CD4+ T-cell depletion correlated with granulomas that contained fewer CD4+ and CD8+ T cells, less interferon γ, more neutrophils, more interleukin 10 (IL-10), and increased M. tuberculosis numbers. M. tuberculosis numbers correlated positively with IL-10 and interferon α levels and fewer CD4+ and CD8+ T cells. ART reduced IL-10 production. CONCLUSIONS: Peripheral CD4+ T-cell depletion correlated with increased M. tuberculosis presence, increased IL-10 production, and other phenotypic changes within granulomas, demonstrating the HIV infection progressively changes these granulomas.
HIVIL-10antiretroviral therapycoinfectiongranulomahistologylymph nodemycobacteriumtuberculosisAdultAgedCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCoinfectionFemaleGranulomaHIV InfectionsHIV-1HumansInterferon-gammaInterleukin-10Lymph NodesMaleMiddle AgedMycobacterium tuberculosisTuberculosisYoung AdultWilkinson, R FC001218Gutierrez FC00109211 Medical and Health Sciences06 Biological SciencesMicrobiology